GALC

galactosylceramidase, the group of Glycoside hydrolases

Basic information

Region (hg38): 14:87837820-87993665

Links

ENSG00000054983 ∙ NCBI:2581 ∙ OMIM:606890 ∙ HGNC:4115 ∙ Uniprot:P54803 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Krabbe disease (Definitive), mode of inheritance: AR
• Krabbe disease (Strong), mode of inheritance: AR
• Krabbe disease (Strong), mode of inheritance: AR
• Krabbe disease (Definitive), mode of inheritance: AR
• Krabbe disease (Definitive), mode of inheritance: AR
• Krabbe disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Krabbe disease	AR	Biochemical	BMT/HSCT have been described, and in presymptomatic infants as well as older mildly-affected individuals, this treatment may improve and preserve cognitive function (ie, presymptomatic transplant has much better neurological outcomes)	Biochemical; Neurologic	14024503; 3123790; 4773865; 1817026; 1817027; 2056315; 1891085; 8297359; 7581365; 9449482; 8940268; 9338580; 9545360; 10833326; 15901860; 16607461; 17579360; 19332366; 21070211; 20301416; 20886637; 22115770; 22704718; 23462331; 23276707; 33832819

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GALC gene.

• Galactosylceramide_beta-galactosidase_deficiency (1254 variants)
• not_provided (276 variants)
• not_specified (78 variants)
• Inborn_genetic_diseases (62 variants)
• GALC-related_disorder (23 variants)
• Intellectual_disability (6 variants)
• See_cases (4 variants)
• EEG_abnormality (2 variants)
• Small_for_gestational_age (2 variants)
• Progressive_visual_loss (2 variants)
• Amblyopia (2 variants)
• Seizure (2 variants)
• Developmental_regression (2 variants)
• EMG:_axonal_abnormality (2 variants)
• Hemiparesis (2 variants)
• Strabismus (2 variants)
• Leukodystrophy (2 variants)
• Fetal_growth_restriction (2 variants)
• Global_developmental_delay (2 variants)
• Dysmyelinating_leukodystrophy (2 variants)
• Status_epilepticus (2 variants)
• Breech_presentation (2 variants)
• Nystagmus (2 variants)
• Spastic_ataxia (2 variants)
• Loss_of_ambulation (2 variants)
• EMG_abnormality (2 variants)
• Neonatal_hypoglycemia (2 variants)
• Incidental_Discovery (1 variants)
• Fabry_disease (1 variants)
• Movement_disorder (1 variants)
• Abnormal_brain_morphology (1 variants)
• Abnormality_of_the_nervous_system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000153.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	8	321	3	333
missense	21	122	323	16	4	486
nonsense	41	34	1			76
start loss		3	2			5
frameshift	81	43	1			125
splice donor/acceptor (+/-2bp)	14	43	2			59
Total	157	246	337	337	7

Highest pathogenic variant AF is 0.0037812707

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GALC	protein_coding	protein_coding	ENST00000261304	17	155846

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124685	0	113	124798	0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.186	365	375	0.973	0.0000193	4447
Missense in Polyphen		124	149.03	0.83204		1770
Synonymous	-0.0698	136	135	1.01	0.00000715	1286
Loss of Function	1.88	29	42.2	0.687	0.00000216	461

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000782	0.000781
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000278	0.000278
Finnish	0.000467	0.000464
European (Non-Finnish)	0.000497	0.000494
Middle Eastern	0.000278	0.000278
South Asian	0.000459	0.000458
Other	0.000497	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon. {ECO:0000269|PubMed:8281145, ECO:0000269|PubMed:8399327}.
• Disease: DISEASE: Leukodystrophy, globoid cell (GLD) [MIM:245200]: An autosomal recessive disorder characterized by insufficient catabolism of several galactolipids that are important for normal myelin production. Four clinical forms are recognized. The infantile form accounts for 90% of cases. It manifests before six months of age with irritability, spasticity, arrest of motor and mental development, and bouts of temperature elevation without infection. This is followed by myoclonic jerks of arms and legs, oposthotonus, hypertonic fits, and mental regression, which progresses to a severe decerebrate condition with no voluntary movements and death from respiratory infections or cerebral hyperpyrexia before 2 years of age. Cases with later onset present with unexplained blindness, weakness and sensorimotor peripheral neuropathy, mental deterioration and death. {ECO:0000269|PubMed:10234611, ECO:0000269|PubMed:10477434, ECO:0000269|PubMed:17579360, ECO:0000269|PubMed:20886637, ECO:0000269|PubMed:23462331, ECO:0000269|PubMed:8595408, ECO:0000269|PubMed:8786069, ECO:0000269|PubMed:8940268, ECO:0000269|PubMed:9272171}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.449

Intolerance Scores

• loftool: 0.252
• rvis_EVS: 0.85
• rvis_percentile_EVS: 88.48

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.407

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

• Biological process: galactosylceramide catabolic process;glycosphingolipid metabolic process;myelination
• Cellular component: lysosome;lysosomal lumen
• Molecular function: galactosylceramidase activity